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Both central sympathoexcitation and peripheral angiotensin II-dependent vasoconstriction contribute to hypertension development in immature heterozygous Ren-2 transgenic rats
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SYSNO ASEP 0555816 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Both central sympathoexcitation and peripheral angiotensin II-dependent vasoconstriction contribute to hypertension development in immature heterozygous Ren-2 transgenic rats Author(s) Řezáčová, Lenka (FGU-C) RID, ORCID, SAI
Vaněčková, Ivana (FGU-C) RID, ORCID
Hojná, Silvie (FGU-C) RID, ORCID
Vavřínová, Anna (FGU-C) RID, ORCID, SAI
Valovič, Pavol (FGU-C) ORCID
Rauchová, Hana (FGU-C) RID, ORCID
Behuliak, Michal (FGU-C) RID, ORCID
Zicha, Josef (FGU-C) RID, ORCID, SAISource Title Hypertension Research. - : Springer - ISSN 0916-9636
Roč. 45, č. 3 (2022), s. 414-423Number of pages 10 s. Language eng - English Country JP - Japan Keywords losartan ; angiotensin II ; intracerebroventricular ; Ren-2 transgenic rats ; hypertension OECD category Physiology (including cytology) R&D Projects GC19-08260J GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support FGU-C - RVO:67985823 UT WOS 000705780600003 EID SCOPUS 85116514489 DOI 10.1038/s41440-021-00775-2 Annotation Recently, we demonstrated that chronic blockade of the renin−angiotensin system (RAS) lowered the blood pressure (BP) of adult Ren-2 transgenic rats (TGR) mainly through the attenuation of central sympathoexcitation. However, the participation of central and peripheral mechanisms in the development of high BP in immature TGR remains unclear. In the present study, 6-week-old heterozygous TGR males were chronically treated with intracerebroventricular (ICV) or intraperitoneal (IP) infusions of the AT1 receptor inhibitor losartan (1 or 2 mg/kg/day) for 4 weeks. The influence of these treatments on sympathetic- and angiotensin II-dependent BP components (BP response to pentolinium or captopril, respectively) as well as on BP response to exogenous angiotensin II were determined to evaluate the participation of central and peripheral RAS in hypertension development. Chronic IP losartan administration (1 or 2 mg/kg/day) lowered the BP of immature TGR by reducing both sympathetic and angiotensin II-dependent BP components. The central action of IP-administered losartan was indicated by a reduced BP response to acute ICV angiotensin II injection. Chronic ICV administration of a lower losartan dose (1 mg/kg/day) reduced only the sympathetic BP component, whereas a higher ICV administered dose (2 mg/kg/day) was required to influence the angiotensin II-dependent BP component. Accordingly, chronic ICV losartan administration of 2 mg/kg/day (but not 1 mg/kg/day) attenuated the BP response to acute intravenous angiotensin II application. In conclusion, central sympathoexcitation seems to play an important role in hypertension development in immature TGR. Central sympathoexcitation is highly susceptible to inhibition by low doses of RAS-blocking agents, whereas higher doses also affect peripheral angiotensin II-dependent vasoconstriction. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2023 Electronic address https://doi.org/10.1038/s41440-021-00775-2
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